Solubility is an important characteristic in assessing a compound's suitability for various applications, including pharmaceutical, environmental, and industrial application. For example, water solubility is an important characteristic for orally-administered pharmaceutical compounds. Typically, empirical methods are used to determine a compound's solubility but these can be an expensive, time-consuming task, particularly, e.g., in the lead optimization phase of a drug discovery project where a multitude of structural and chemical variants of a new molecular entity (NME) are possible.
Today, computational simulations are used to assist solving a variety of chemical and biochemical problems, such as in computer-aided drug design where computational simulations are used to predict, e.g., whether a given molecule will bind to a target and if so how strongly. A reliable, accurate computational method for predicting compound solubility would be a desirable alternative or complement to conventional empirical approaches. In addition, the ability of the method to provide a structural explanation for the predicted solubility of a compound may facilitate the design of variants with improved solubility.